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Our current research projects include:
Quantification of cardiac radio-frequency ablation
Atrial fibrillation (AF) is an abnormal heart rhythm (arrhythmia) characterized by rapid and irregular beating of the atrial chambers of the heart. It is affecting 2.7-6.1 million people in US. Radiofrequency (RF) ablation (RFA) is commonly used to treat AF. However, the procedure has a high AF recurrence. The indirect information (impedance, temperature, and contact force) used to guide the creation of RF lesions is insufficient to quantify the lesion quality. Too deep a lesion will impair cardiac function, while too shallow a lesion will allow the tissue to heal and restart improper electrical conduction. Our lab is working on monitoring the lesion formation in myocardium with a polarization sensitive-OCT catheter integrated RFA catheter to guide RFA procedure to improve lesion quality and procedure outcome. Challenges include monitoring the catheter-tissue contact and quantify lesion quality on healthy and diseased tissue.
Non-contact assessment of corneal mechanics
Corneal mechanical properties play into our understanding of both disease (such as keratoconus, affecting 1 in 300 people) and surgical intervention. Using a modified version of dynamic light scattering (DLS) optical coherence tomography (OCT), we may assess the relative corneal mechanical properties of a patient in a non-contact manner.
Elastography of embryonic soft tissues
There is compelling evidence to suggest that the stiffness of embryonic strongly effects the future development of the embryo. We seek to better understand the interplay of developmental form and function by developing techniques sensitive enough to determine the material properties of microscopic embryonic tissues. The determination of small-scale material properties is a quickly developing field and our lab is exploring several methods, including optical coherence elastography and micromechanical assays, to interrogate these properties.
Developmental electro-physiology with optical mapping
4D optical mapping is used to study the conduction patterns and propagation of the action potential in embryonic hearts. We hope that a better understanding of the development of cardiac conduction will lead to better treatments for developing heart conditions.
Electrical conduction wave of a HH stage 15 avian embryonic heart. Colors indicate relative action potentials in arbitrary units. The leading yellow band represents a 10 ms activation region. Unpublished. Video credit to Pei Ma.
Congenital heart disease studies
Our lab, along with our collaborators, use optical methods to study the cause, development, and treatment for congenital heart disease. Diseases we have studied include fetal alcohol syndrome and cardiac neural crest cell ablation (DiGeorge Syndrome). After a disease model is established, it is possible to test treatments that may reverse some of the harmful effects of the disease or halt its progression. For instance, we have seen a significant reduction in mortality and morbidity in FAS-model embryos given a betaine treatment. We are hopeful that these results may one day translate to clinical applications.
This video shows a comparison of a cardiac neural crest cell (CNCC) ablated quail embryo (HH 19) and a normal quail embryo (HH 19). Unpublished. Video credit to Pei Ma and Brecken Blackburn.
Structure and function relationships in early hearts
There is limited knowledge about the properties of blood flow, tissue shear stress, and the development of various structures in the heart. OCT and other optical methods can help elucidate the relationships between these factors to present a more complete picture of cardiac development.
Four-dimensional (4D) Doppler OCT imaging of the beating stage 17 quail heart under normoxia (left) and hypoxia (5% oxygen for 1 hr, right). The pulsed Doppler waveform is displayed on top, and the color Doppler (red and blue) is overlaid on top of the OCT image of the heart (orange). The inflow region is on the left and the outflow region is on the right in each image. The red color indicates that the blood flow is away from the light beam (flow is top-to-bottom); and the blue color indicates the opposite. Pulsed Doppler images were generated from both the inflow region (top trace) and the outflow region (bottom trace), and the vertical bars represent the synchronization to the 4D images. Gu, Shi, et al. "Optical coherence tomography captures rapid hemodynamic responses to acute hypoxia in the cardiovascular system of early embryos." Developmental Dynamics 241.3 (2012): 534-544.
Our methods include:
Light sheet microscopy
The light sheet microscope illuminates a plane of the sample with a fluorescence sheet of light, while imaging of the sample occurs orthogonally. By using a scanning sheet instead of a scanning point (as in confocal microscopy), light sheet microscopy can be performed hundreds of times faster than traditional microscopy methods. Our lab has used this method to capture the electro-physiology of embryonic hearts.
Optical Coherence Tomography
Optical coherence tomography (OCT) is a method, first described in 1990, which can image several millimeters into a sample with 10µm resolution. By sending low-coherence light into a sample and interfering the reflection with a reference beam, the structure of the sample can be determined. Multiple scans are stitched together to create volumetric images.
Optical Coherence Microscopy
OCM is much like OCT, but has a higher resolution (around 2µm).
Optical Mapping
Optical mapping is used to study electro-physiology. This system is similar to a fluorescence microscope, but is able to image at high speeds and is sensitive to the small changes that correspond to the membrane potentials (action potentials) in a sample. A voltage-sensitive fluorescent dye is applied to the sample to make the action potentials visible.
Avian embryo models
To study development, our lab commonly uses a quail model. Quails are an excellent model because they (1) hatch within 18 days, (2) are a self-contained system, so teratogens may be introduced in known quantities without concern for the mother's metabolism, (3) are relatively easy to use in high-throughput experiments, and (4) exhibit a development similar to mammals, especially in regards to cardiac development, as they also have a four-chambered heart.
For our most recent papers, please see PubMed
